Prevalence of Congenital Anomalies in Iran: A Review Article.

BACKGROUND
Congenital anomalies are considered as main causes of disability and mortality among children in developing and developed countries. Expenditures of hospitalization and treatment procedures for these children impose a large burden on health system and their families. This study aimed to review the prevalence of congenital anomalies among infants in Iran.


METHODS
The review of studies was conducted through searching databases including IranMedex, SID, Magiran, Scopus, and PubMed. Descriptive and cross-sectional studies investigating on the prevalence of congenital anomalies among infants were included into the study. Hand search for some related journals and websites was done. The list of studies' references was reviewed. The data were analyzed using the CMA 2 software.


RESULTS
Of 455 studies, 27 studies were included into the meta-analysis study. The studies were conducted between 1992 and 2014.The overall prevalence of congenital anomalies among infants was estimated to be 2.3%. The overall prevalence rates, in terms of gender, were estimated to be 3% in boys and 2% in girls. While the highest prevalence rates were related to musculoskeletal anomalies (27.5%), skin anomalies (19.7%) and genitourinary system anomalies (15.8%), the lowest prevalence rate was related to respiratory system (1.82%).


CONCLUSION
The prevalence of congenital anomalies among infants in Iran is high. In order to reduce the rates of these anomalies and complications resulted from them, coping and preventive strategies such as the necessity of genetic counseling particularly in consanguineous marriages seem to be appropriate solutions.


Introduction
Today's babies will constitute future young generation and capital in any country depends on healthy and fecund youths, thus their health will guarantee this great capital. Congenital anomalies will be of main factors of ineffectiveness of this great human capital, particularly if they are not diagnosed and treated from the beginning (1,2). Congenital anomalies are considered as main causes of disability and mortality among children in developing and developed countries. Expenditures of hospitalization and treatment procedures for these children impose a large excess burden on health system and their families (3,4). This type of anomalies according to definition by WHO includes single or several structural, functional or biochemical and molecular anomalies identified and diagnosable at birth (5). Anomalies based on the intensity are divided into two cate-gories: major and minor. Major anomalies are defined as anatomical anomalies that affect an individual's life and natural performance. Minor anomalies are referred to structural changes that do not require treatment or can be improved through simple methods (6). Defects at birth are the main cause of infant mortality; therefore, 21% of mortality during infancy results from these anomalies. This type of anomalies is the fifth leading cause of reduced life expectancy before the age of 65 and is one of the main reasons for disabilities. Two to three percent of newborns have serious structural anomalies at birth and these anomalies are diagnosed in other 2%-3% of infants by the end of the fifth year that constitutes a total of 4%-6% (7). Although various factors have been identified as factors affecting congenital anomalies (including genetic and environmental factors, teratogens such as mother's addiction to alcohol, diabetes, malnutrition, infection, hyperthermia, drug use and exposure to chemicals or radioactive), 66% of anomalies occur with unknown causes (3,8). Furthermore, one of health issues in the country is the existence of congenital anomalies and disorders related to consanguineous marriage, which impose a large financial burden on the country and mental and economic burden on family. Those who have these anomalies not only deal with pain and suffering in their life but also impose a large burden of economic and social hardships on their families and society (9). In general, treatment and rehabilitation of disabled people due to congenital anomalies impose large costs on a society and desired results for person with disability and society are not always obtained. Furthermore, some severe congenital anomalies cause miscarriage or intrauterine fetal death. The identification and prevention of the incidence of congenital anomalies are more costeffective for societies rather than the treatment or rehabilitation (10) and any serious effort to identify factors affecting congenital anomalies and to prevent them will lead to make the more health and well-being for future generation and to avoid socio-economic harms (3).
The prevalence of the more congenital anomalies in infants born alive throughout the country imposes mental and physical pain and suffering on these patients and their families; increases their treatment costs in various ages of their life, and decreases quantity of productive human resources in the society. The current study aimed to review the prevalence of congenital anomalies in infants.

Methods
The reviewed documents consist of descriptive and cross-sectional studies selected through searching databases including IranMedex, SID, Magiran, Scopus, and Pubmed, with no time limit. The method of searching studies was mainly done using valid keywords related to prevalence, anomaly and congenital. In the next step, the identified studies were reviewed and appropriate studies were selected based on inclusion criteria. The inclusion criteria in this study included descriptive and cross-sectional studies on the prevalence of congenital anomalies among infants in Iran; studies were in English and Persian, with no time limit. The exclusion criteria included those studies that mentioned just one specific congenital anomaly (such as the prevalence of Clubfoot congenital deformity); studies that investigated the prevalence of congenital anomalies in infants among a specific group of mothers (such as mothers suffering from Insulin-dependent diabetes); qualitative studies, studies presented in conferences; and interventional studies. The search in any database was done through searching titles and abstracts in a way that all studies and abstracts in which the words congenital anomaly and factors affecting anomaly were mentioned in their titles, were selected. Then the titles of all studies searched the databases were listed. The list of selected studies was screened in order to identify the most appropriate ones to the issue and studies with repeated titles were excluded. The reference management software (Endnote X6) was used to organize, remove duplicates and assess titles of abstracts. Finally, two authors reviewed the abstracts and full-texts of studies based on the inclusion crite-ria. The STROBE checklist (11,12) was used to assess the quality of the identified studies and the studies of high quality were selected. For meta-analysis, meta-analysis statistical techniques were used to calculate the overall prevalence and the data were analyzed using the CMA: 2 software. The I 2 index was used to test the heterogeneity of the studies; since the difference of prevalence rates in various studies was high (heterogeneity of the studies), the random effect model with 95% confidence interval was used.

Results
Twenty-six studies were selected for metaanalysis ( Table 1). The studies were conducted between 1992 and 2014 in Iran. Overall, 215756 infants had been investigated in the total of studies. The results showed that the prevalence of congenital anomalies among infants varied from 0.4% in Babol to 5.5% in Zanjan, Iran. The overall prevalence in Iran, among boys, and the girls were estimated to be 2.3%, 3%, and 2%, respectively. The highest prevalence rates of anomalies respectively were related to musculoskeletal anomalies (27.5%), skin anomalies (19.7%) and genitourinary system anomalies (15.8%). The lowest prevalence of anomalies was related to respiratory system (1.82%). The ratio of anomalies in boys (58.3%) was higher than in girls (41.1%). Fig. 1 shows the flowchart for the identification of studies. Poor quality of article in assessing: 7
Overall, 95% CI for the prevalence was drawn for each study in the horizontal line format (Q=28.4, df = 11, P<0.001, I 2 = 61.3). The result of funnel plot show there was possibility publication bias among studies (Fig. 5, 6).

Discussion
The results of this study showed that the overall prevalence of congenital anomalies among infants in Iran is 2.3%; and its prevalence rate was estimated to be higher in boy infants (3%), than girl infants (2%). The highest prevalence rates of anomalies respectively were related to musculoskeletal anomalies (27.5%), skin anomalies (19.7%) and genitourinary system anomalies (15.8%), while the lowest prevalence of anomalies was related to respiratory system (1.82%). The prevalence rates of anomalies are different among the studied populations and in various body systems and organs. Genitourinary system anomalies were followed by musculoskeletal anomalies as the most prevalent anomalies (13). However, findings of the studies (7,14), similar to the current study, show that the most prevalent anomaly is related to musculoskeletal system.
In addition, in Bahrain, the highest prevalence rates of anomaly are related to musculoskeletal system diseases (2.28) and genitourinary system diseases (2.13) (15). Through a simple review of the documents, the reason for such a difference in the prevalence of all types of congenital diseases in reports of different studies can be the difference in the prevalence of serious congenital anomalies among various races which environmental factors sometimes have impact on their incidence (16). The percentage of the prevalence of congenital anomalies among infants in Iran (2.3%) is lower than that of some studies conducted in other countries in the world. The rates of congenital anomalies were reported to be 7.6% in Uganda (17) (23) which is close to the estimated prevalence rate of anomaly in Iran. However, the prevalence rates of anomalies in Lebanon (1.65%) (24) and in China (1.54%) (25) are lower than the estimations in Iran. The difference in the prevalence rates of congenital anomalies in different parts of the country and the world can be due to differences in genetic, racial, cultural and socio-economic factors among individuals and the assessment method of infants. The difference in methods used for diagnosing anomalies and characteristics of studied populations (live or dead babies) can be a reason for part of this difference (26-28). There is relationship between many congenital anomalies and gender of infant; and the relationship between each of these anomalies and gender of infant should be considered in further larger studies (29). In the current study, the prevalence of anomalies among boys (58.3%) was higher than among girls (41.1%). Suffering from congenital anomalies in a study conducted in the Czech Republic in 2000 and also in a study in 1980, similar to the results of the current study, was higher among boy infants than girl infants (30).
In order to prevent the birth of infants with severe congenital anomalies and given the necessity of healthy, productive and effective future generation of human resources in the society, the necessity of genetic counseling especially in consanguineous marriage and care initiatives for pregnant mothers is of particular importance.

Conclusion
The prevalence of congenital anomalies in different body systems in infants is high. Even if infants born with these anomalies can survive for years, they will live all their lifelong with complications and hardships due to these diseases. Moreover, their families also face heavy cost incurred on improving and reducing effects of these anomalies in their children. Thus, in order to prevent the birth of such infants the necessity of genetic counseling especially in consanguineous marriage is recommended. Furthermore, caring before, during and after pregnancy including healthy nutrition, proper exercise, mother's lack of exposure to dangerous rays and radiations and avoiding stress and anxiety can play a useful role in the birth of healthy and normal infants.

Ethical considerations
Ethical issues (Including plagiarism, informed consent, misconduct, data fabrication and/or falsification, double publication and/or submission, redundancy, etc.) have been completely observed by the authors.